Usefulness of urine dipstick test in the management of adverse events associated with immune checkpoint inhibitors.

PURPOSE: The usefulness of urine dipstick tests (UDTs) in patients with diabetes has been reported. The aim of the present study was to investigate the utility of self-performed UDTs and patient diaries in the management of impaired glucose tolerance, one of the adverse events of immune checkpoint inhibitors (ICIs). METHODS: Patients receiving ICIs underwent self-checks with UDTs twice a week for up to 6 months. Pharmacists checked the results at every patient visit, and by phone every 3 months. The primary endpoint was to prospectively assess whether symptoms recorded in patient diaries and UDTs could reduce unscheduled hospital admissions due to impaired glucose tolerance. The secondary endpoint was the correlation between the symptoms in the patient diaries and UDT results. RESULTS: A total of 112 patients were enrolled in the study. Out of the 3197 planned self-UDTs, 3128 (97.8%) were performed. Forty-four patients (39.3%) were admitted to the hospital, two (1.8%) of whom were admitted due to abnormal glucose tolerance, with one having a positive UDT. There were 46 unscheduled outpatient visits (41.1%), of which five (4.5%) were due to abnormal glucose tolerance symptoms and four were due to a positive UDT. The correlation between descriptions of fatigue or dry mouth in the patient diaries and positive glucose UDTs was 52.4% in sensitivity and 62.4% in specificity. CONCLUSION: Self-monitoring of symptoms and self-performing of UDTs could not reduce the emergency hospitalization rate. However, this approach could be effective in the objective monitoring of patient status, especially regarding glucose intolerance occurrences.

Trace proteinuria detected via dipstick test is associated with kidney function decline and new-onset overt proteinuria: the Japan Specific Health Checkups (J-SHC) Study.

BACKGROUND: Microalbuminuria is associated with mortality, cardiovascular disease, and end-stage kidney disease. The association between trace proteinuria (detected via dipstick test) and kidney outcomes is unclear. METHODS: This nationwide longitudinal study used data from the Japan Specific Health Checkups Study conducted during 2008-2014. The frequency of trace proteinuria (detected via dipstick test) during first two visits was used as an exposure variable (TrUP 0/2, no trace proteinuria; TrUP 1/2, detected once; TrUP 2/2, detected twice), and kidney outcomes were evaluated. The association between the frequency of trace proteinuria and incidence of 1.5-fold increase in serum creatinine levels and overt proteinuria was analyzed using Cox regression analysis. Trajectories of estimated glomerular filtration rate (eGFR) were compared using a mixed-effect model. RESULTS: Among 306,317 participants, 3188 and 17,461 developed a 1.5-fold increase in serum creatinine levels and new-onset overt proteinuria, respectively, during the median follow-up period of 36.2 months. The adjusted hazard ratio (HR) and 95% confidence interval (CI) for 1.5-fold increase in serum creatinine level in the TrUP 1/2 and TrUP 2/2 groups, compared to TrUP 0/2 group, were 1.23 (1.07-1.42) and 1.39 (1.01-1.92), respectively, and the adjusted HR (95% CI) for overt proteinuria were 2.94 (2.83-3.06) and 5.14 (4.80-5.51), respectively. The eGFR decline rates in the TrUP 1/2 and TrUP 2/2 groups were higher than that in the TrUP 0/2 group (p for interaction < 0.001). CONCLUSIONS: Trace proteinuria (detected via dipstick test) was associated with subsequent kidney function decline and overt proteinuria in the general population.

The Level of Urine Dipstick Proteinuria and Its Relation to the Risk of Incident Cholelithiasis.

BACKGROUND: Previous studies have suggested the potential association between renal diseases and gallstone. The extent of proteinuria is recognized as a marker for the severity of chronic kidney disease. However, little data is available to identify the risk of incident gallstone according to the level of proteinuria. METHODS: Using a data of 207,356 Koreans registered in National Health Insurance Database, we evaluated the risk of gallstone according to the levels of urine dipstick proteinuria through an average follow-up of 4.36 years. Study subjects were divided into 3 groups by urine dipstick proteinuria (negative: 0, mild: 1+ and heavy: 2+ or greater). Multivariate Cox-proportional hazard model was used to assess the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident cholelithiasis according to urine dipstick proteinuria. RESULTS: The group with higher urine dipstick proteinuria had worse metabolic, renal, and hepatic profiles than those without proteinuria, which were similarly observed in the group with incident cholelithiasis. The heavy proteinuria group had the greatest incidence of cholelithiasis (2.39%), followed by mild (1.54%) and negative proteinuria groups (1.39%). Analysis for multivariate Cox-proportional hazard model indicated that the heavy proteinuria group had higher risk of cholelithiasis than other groups (negative: reference, mild proteinuria: HR 0.97 [95% CI, 0.74-1.26], and heavy proteinuria: HR 1.46 [95% CI, 1.09-1.96]). CONCLUSION: Urine dipstick proteinuria of 2+ or greater was significantly associated with increased risk for incident gallstone.

Role of dipstick proteinuria for predicting cardiovascular events: a Japanese cardiovascular hospital database analysis.

Initial screening for proteinuria by urine dipstick test (UDT) may be useful for predicting clinical outcomes. The Shinken Database includes all the new patients visiting the Cardiovascular Institute Hospital in Tokyo, Japan. Patients for whom UDT was performed at their initial visit between 2004 and 2010 (n = 7131) were divided into three groups according to the test results: negative, trace, and positive (1+ to 4+) proteinuria. During the mean follow-up period of 3.4 years, 233 (3.1%) deaths, 255 (3.6%) heart failure (HF) events, and 106 (1.5%) ischemic stroke (IS) events occurred. Prevalence of atherothrombotic risks increased with an increase in the amounts of proteinuria. The incidence of all-cause death, HF and IS events increased significantly from negative to trace to positive proteinuria groups (log rank test, P for trend < 0.001). Multivariate analysis revealed independent association between proteinuria and all-cause death [hazard ratio (HR): 1.50, 95% confidence interval (CI) 1.07-2.10], HF (HR: 1.55, 95% CI 1.14-2.12), and IS (HR: 2.08, 95% CI 1.26-3.45). Even trace proteinuria was independently associated with HF (HR: 1.64, 95% CI 1.07-2.53) and IS (HR: 2.17, 95% CI 1.14-4.11) and with all-cause death (HR: 1.56, 95% CI 0.99-2.47). In conclusions, dipstick proteinuria was independently associated with cardiovascular events and death, suggesting that the UDT is a useful tool for evaluating patients' risk for such adverse events.

Usefulness of the quantitative measurement of urine protein at a community-based health checkup: a cross-sectional study.

BACKGROUND: The dipstick urinalysis for proteinuria has been used for chronic kidney disease (CKD) screening at community-based health checkups; however, it has major drawbacks in that the result is only semi-quantitative and is influenced by urine concentration. METHODS: We conducted urine protein/creatinine ratio (UPCR) measurements of 590 participants who showed a result of more than trace proteinuria on a dipstick analysis and evaluated the usefulness of UPCR measurements in community-based health checkups. RESULTS: The UPCR values increased in accordance with the severity of the dipstick test findings, but statistical significance was only obtained between (±) and (1+), between (±) and (2+), and between (±) and (3+) groups. When the participants with (±) proteinuria were subjected to CGA classification (a classification of CKD by cause, glomerular filtration rate category, and albuminuria category) according to their UPCR data, a significant proportion of subjects (277, 77.0%) moved from the A2 category into A1, which is a less severe category. Conversely, 21 subjects (5.8%) were reclassified into a more severe category (A3). Thus, a dipstick test may produce a non-negligible number of false negatives as well as a large number of false positives. Similarly, the classifications of more than half of the subjects with (1+) or more severe proteinuria were changed based on their UPCR results. CONCLUSION: The dipstick urinalysis for proteinuria appears less reliable than expected, suggesting that the quantitative measurement of urine protein should be performed even during mass health checkups to ensure the early detection and prevention of CKD.

Regional variance in the use of urine dipstick test for outpatients in Japan.

AIM: The urine dipstick is a simple diagnostic module for detecting proteinuria, haematuria and glycosuria and is favourably accepted in East Asia despite debates regarding its accuracy and target population, claiming that quantitative tests for a high-risk cohort should be more cost-effective. However, the current status of utilizing this test in these countries is not widely known due to lack of extensive data. We aimed to clarify the current nationwide and regional status of utilization of the urine dipstick test in an outpatient care setting and to determine the regional factors associated with adoption of this method. METHODS: This cross-sectional study used openly accessible data from the national claim database that included the health insurance claims data of the Japanese population in 2017. RESULTS: In total, 67 125 386 urine dipstick tests were performed compared with 1 862 700 quantitative urine protein tests and 17 544 949 urine sediment microscopy tests. Dipstick tests were employed principally for those who are >65 years old (60.3%) and, although the male population (52.5%) is generally larger, the female population is larger in age of 15 to 39 years and >85 years. Multivariate analysis with several regional parameters revealed that the test was performed more commonly in the areas that accommodate greater elderly population (P < .01). CONCLUSION: Despite a heated dispute, the urine dipstick test is performed even more frequently than the quantitative biochemical or microscopic sediment tests, especially in regions holding the larger elderly population, which suggests that the test forms a part of geriatric medical care.

Chronic renal dysfunction, proteinuria, and risk of Parkinson's disease in the elderly.

BACKGROUND: The roles of chronic kidney disease and proteinuria in the development of Parkinson's disease have not been widely studied. The objective of this study was to examine the associations of chronic renal dysfunction and proteinuria with the risk of PD in older adults using cohort data of the whole South Korean population. METHODS: We included 3,580,435 individuals aged ≥65 years who had undergone health checkups provided by the National Health Insurance Service of South Korea between 2009 and 2012 and were followed until 2015. Multivariable Cox proportional hazards regression models were performed. RESULTS: During a mean follow-up of 5.2 ± 1.3 years, 30,813 individuals (0.86% of the total population) developed PD. Lower estimated glomerular filtration rate and a higher degree of proteinuria on a dipstick test were associated with higher incidence probability of PD (log-rank P < 0.001). In Cox regression models, chronic renal dysfunction graded by estimated glomerular filtration rate (mL/min/1.73 m2 ) was associated with increased risk of PD after adjusting for potential confounding variables; hazard ratio (95% confidence interval) was 1.13 (1.10-1.17) for estimated glomerular filtration rate 60-90, 1.36 (1.31-1.42) for estimated glomerular filtration rate 30-60, and 1.47 (1.32-1.63) for estimated glomerular filtration rate <30 (P for trend <0.001). Proteinuria ≥1+ was also associated with increased risk of PD development (hazard ratio, 1.12; 95% confidence interval, 1.06-1.18). Coexistence of chronic kidney disease and proteinuria showed an increased hazard ratio of 1.33 (95% confidence interval, 1.23-1.45) for PD occurrence. CONCLUSIONS: Our findings suggest that chronic renal dysfunction and dipstick-positive proteinuria may be independent risk factors for the development of PD in older adults. © 2019 International Parkinson and Movement Disorder Society.

Voltammetric analysis for fast and inexpensive diagnosis of urinary tract infection: a diagnostic study.

BACKGROUND: Dipstick test is widely used to support the diagnosis of urinary tract infections (UTI). It is effective in ruling out UTI, but urine culture is needed for diagnosis confirmation. In this study we compared the accuracy of voltammetric analysis (VA) with that of DT to detect UTI (diagnosed using urine culture), and its usefulness as a second-stage test in people with positive DT. METHODS: 142 patients were enrolled with no exclusion criteria. VA was performed using the BIONOTE device. Partial Least Square Discrimination Analysis was used to predict UTI based on VA data; diagnostic performance was evaluated using sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively), positive and negative likelihood ratios (LR), accuracy, diagnostic odds ratio (DOR). RESULTS: Mean age was 76.6 years (SD 12.6), 57% were male. VA had a better overall performance respect to DT in detecting UTI with accuracy 81.7% vs 75.9%, specificity 90.8% vs 82.5%, PPV 75% vs 61.4%, positive LR 6.68 vs 3.5, DOR 17.7 vs 7.47; sensibility, NPV and negative LR of the two tests were similar. VA had an accuracy of 82.4% in discriminating bacterial from fungal infections. When added as a second-stage test, VA identified 9 of the 17 false positive patients, with a net specificity of 91.7%, sensitivity 54%, PPV 75% and NPV 81%. CONCLUSIONS: VA is a quick and easy method that may be used as a second stage after DT to reduce the number of urine culture and of inappropriate antibiotic prescriptions.

Trace Urine Albumin and Mortality: Kangbuk Samsung Health Study.

BACKGROUND/AIMS: The importance of a trace albumin on the urine dipstick test is not well known and is frequently disregarded in clinical practice. The aim of this study is to investigate the role of trace albuminuria in predicting all-cause mortality in Korean adults. METHODS: In this retrospective cohort study, we analyzed 347,938 Korean adults who underwent urine dipstick test from 2002 to 2012 in a health examination program. The participants were divided into three groups according to dipstick negative, trace (±), and overt (≥1+) albuminuria. The trace group was further stratified by urine specific gravity (SG) and classified as either high (≥1.020) or low (≤1.015) SG. Mortality data was obtained from STATICS KOREA, a Korean federal statistical organization. RESULTS: During a median follow-up period of 5.9 years, 1,855 deaths occurred. Mortality was compared to negative group and adjusted for potential risk factors. Mortality did not increase in the trace group (HR, 1.19; 95% CI, 0.97-1.47; P=0.097), but increased in the overt (HR, 1.69; 95% CI, 1.38-2.07; P< 0.001) albuminuria group. When the trace group was subdivided according to urine SG, mortality did not increase in the high SG (HR, 1.09; 95% CI, 0.86-1.37; P=0.488) group, but increased in the low SG (HR, 1.84; 95% CI, 1.19-2.83; P=0.006) and overt (HR, 1.70; 95% CI, 1.39-2.08; P< 0.001) groups. CONCLUSION: Trace albumin with low SG in urine dipstick test was associated with higher all-cause mortality in Korean adults. We should not neglect the significance of trace albumin and SG when interpreting urinalysis results.

Establishing cut-offs for urine erythrocyte and leukocyte dipstick tests.

Urine erythrocyte (Ery) and leukocyte (Leu) dipstick tests are essential for detecting microhematuria and urinary tract infection. Currently, there is no suggestion for establishing the cut-off limits in an ordinal scale test. This study aimed to establish the cut-off limits for urine Ery and Leu dipstick tests via probit regression. From 1 January 2016 to 30 June 2016, laboratory data were collected from patients at one teaching hospital whose specimen had analytical results from both a urine dipstick test and an automated urine particle analyzer. Probit regression was used to estimate the probability of positive urine dipstick results as a function of log-transformed urine Ery and Leu concentrations. Based on the analysis of 22,122 specimens, the estimated concentration that yields 50% positive results (C50) of the Ery weak+, 1+, 2+, 3+, and 4 + dipstick results were 14.6, 40.4, 51.6, 136.3 and 219.0 × 106/L, respectively. The estimated C50 of the Leu 1+, 2+ and 3 + dipstick results were 22.7, 67.9 and 283.9 × 106/L, respectively. The estimated values were different from arbitrary concentrations provided for each dipstick category by the manufacturer. If a quantitative comparison method/procedure is available, the cut-off limits of an ordinal scale test can be established using probit regression. Each laboratory should investigate the transferability of the arbitrary concentrations provided by the manufacturer, and if necessary, determine its own cut-off limits of urine Ery and Leu dipstick tests.

Rapid dipstick detection of Vibrio cholerae in household stored and municipal water in Dhaka, Bangladesh: CHoBI7 trial.

OBJECTIVE: In urban Dhaka, Bangladesh, 30% of source water samples collected from the households of patients with cholera had detectable Vibrio cholerae. These findings indicate an urgent need for a public health intervention for this population. The Crystal VC® dipstick test is a rapid method for detecting V. cholerae in stool and water. However, to date no study has investigated the use of the rapid dipstick test for household surveillance of stored drinking water. METHODS: The efficacy of the Crystal VC® dipstick test for detecting V. cholerae in the Dhaka city municipal water supply and stored household drinking water sources after enrichment for 18 h in alkaline peptone water (APW) was compared to bacterial culture as the gold standard. RESULTS: A total of 1648 water samples (824 stored household drinking water samples and 824 municipal water supply samples) were collected from households of patients with cholera. The overall specificity and sensitivity of the dipstick test compared to bacterial culture was 99.6% (95% confidence interval (CI): 99.2%, 99.9%) and 65.6% (95% CI: 55.2%, 75%), respectively. The specificities for stored household drinking water and Dhaka city municipal supply water compared to bacterial culture were 99.8% (95% CI: 99.1%, 100%) and 99.5% (95% CI: 98.6%, 99.9%), respectively (P = 0.138), and the sensitivities were 66.7% (95% CI: 43.0%, 85.4%) and 65.3% (95% CI: 53.5%, 76.0%), respectively (P = 0.891). CONCLUSION: The Crystal VC® dipstick is a promising screening tool for cholera outbreak surveillance in resource-limited settings where elimination of false-positive results is critical. The lower than expected sensitivity should be further investigated in future studies.

The influence of vitamin C on the urine dipstick tests in the clinical specimens: a multicenter study.

BACKGROUND: Vitamin C may interfere with the results of urine dipstick tests. We investigated the incidence of urinary vitamin C and its interference with urine dipstick reagents using a vitamin C dipstick. METHODS: The incidence of urinary vitamin C was determined in patients and healthy individuals undergoing routine medical check-ups. Interference tests were performed using samples with various amounts of added vitamin C. For clinical samples, we identified false-negative dipstick glucose, hemoglobin, and leukocyte esterase results based on the urine sediment and serum glucose results. RESULTS: Vitamin C was found in the urine of 18.1% of the subjects overall, and 23.1% of those undergoing medical check-ups. Dipstick results for glucose, leukocyte esterase, and hemoglobin differed between samples without vitamin C and with added vitamin C. When vitamin C was detected in clinical urine samples, 42.3%, 10.6%, and 8.2% of the glucose, hemoglobin, and leukocyte esterase dipstick tests were rated as false negative, respectively. CONCLUSIONS: Vitamin C was frequently found in clinical urine samples, and its concentration was higher in individuals undergoing medical check-ups. Urinary vitamin C can interfere with the urine dipstick results. This study gives useful information for predicting false-negative rates of urine dipstick tests caused by vitamin C.

Opportunities and challenges for the application of microfluidic technologies in point-of-care veterinary diagnostics.

There is a growing need for low-cost, rapid and reliable diagnostic results in veterinary medicine. Point-of-care (POC) tests have tremendous advantages over existing laboratory-based tests, due to their intrinsic low-cost and rapidity. A considerable number of POC tests are presently available, mostly in dipstick or lateral flow formats, allowing cost-effective and decentralised diagnosis of a wide range of infectious diseases and public health related threats. Although, extremely useful, these tests come with some limitations. Recent advances in the field of microfluidics have brought about new and exciting opportunities for human health diagnostics, and there is now great potential for these new technologies to be applied in the field of veterinary diagnostics. This review appraises currently available POC tests in veterinary medicine, taking into consideration their usefulness and limitations, whilst exploring possible applications for new and emerging technologies, in order to widen and improve the range of POC tests available.

Comparison between urine albumin-to-creatinine ratio and urine protein dipstick testing for prevalence and ability to predict the risk for chronic kidney disease in the general population (Iwate-KENCO study): a prospective community-based cohort study.

BACKGROUND: This study compared the combination of estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) vs. eGFR and urine protein reagent strip testing to determine chronic kidney disease (CKD) prevalence, and each method's ability to predict the risk for cardiovascular events in the general Japanese population. METHODS: Baseline data including eGFR, UACR, and urine dipstick tests were obtained from the general population (n = 22 975). Dipstick test results (negative, trace, positive) were allocated to three levels of UACR (<30, 30-300, >300), respectively. In accordance with Kidney Disease Improving Global Outcomes CKD prognosis heat mapping, the cohort was classified into four risk grades (green: grade 1; yellow: grade 2; orange: grade 3, red: grade 4) based on baseline eGFR and UACR levels or dipstick tests. RESULTS: During the mean follow-up period of 5.6 years, 708 new onset cardiovascular events were recorded. For CKD identified by eGFR and dipstick testing (dipstick test ≥ trace and eGFR <60 mL/min/1.73 m(2)), the incidence of CKD was found to be 9 % in the general population. In comparison to non-CKD (grade 1), although cardiovascular risk was significantly higher in risk grades ≥3 (relative risk (RR) = 1.70; 95 % CI: 1.28-2.26), risk predictive ability was not significant in risk grade 2 (RR = 1.20; 95 % CI: 0.95-1.52). When CKD was defined by eGFR and UACR (UACR ≥30 mg/g Cr and eGFR <60 mL/min/1.73 m(2)), prevalence was found to be 29 %. Predictive ability in risk grade 2 (RR = 1.41; 95 % CI: 1.19-1.66) and risk grade ≥3 (RR = 1.76; 95 % CI: 1.37-2.28) were both significantly greater than for non-CKD. Reclassification analysis showed a significant improvement in risk predictive abilities when CKD risk grading was based on UACR rather than on dipstick testing in this population (p < 0.001). CONCLUSIONS: Although prevalence of CKD was higher when detected by UACR rather than urine dipstick testing, the predictive ability for cardiovascular events from UACR-based risk grading was superior to that of dipstick-based risk grading in the general population.

Underestimating chronic kidney disease by urine dipstick without serum creatinine as a screening tool in the general Japanese population.

BACKGROUND: It is not known if urine dipstick alone can identify chronic kidney disease (CKD) in the general Japanese population. METHODS: We designed a cross-sectional study using data obtained in 2008 from a nationwide community-based health examination program for adults aged 40-74. The data consisted of blood tests, urine tests and questionnaire related to metabolic disorders. Those who had both serum creatinine measured and urine dipstick tested were analyzed. RESULTS: Data were obtained from 538,846 people with a mean age of 62.8 years, consisting of 41.6 % males. Our study showed that 14.4 % had an eGFR below 60 mL/min/1.73 m(2), 5.2 % had proteinuria and 18.1 % had CKD. Within the population with CKD, non-proteinuric CKD accounted for 71.4 %. The proportion of non-proteinuric CKD was highest in stage G3a (91.8 %) followed by G3b (77.0 %) disease, and was greater in the more elderly and in females. The proportion of non-proteinuric CKD was 47.9 % in diabetes mellitus, 69.3 % in dyslipidemia, 66.8 % in hypertension and 57.1 % in metabolic syndrome. Furthermore, non-proteinuric CKD accounted for 78.1 % of the population without these lifestyle diseases, suggesting that even in the population without apparent risk, CKD is still prevalent and can be missed when urine dipstick is the only screening method used. CONCLUSIONS: This study showed that a considerable population of CKD might be overlooked when only dipstick proteinuria is assessed for CKD screening. Hence, we strongly recommend that both urinalysis and serum creatinine measurement should be a part of the nationwide CKD screening system.

Evaluation of enrichment method for the detection of Vibrio cholerae O1 using a rapid dipstick test in Bangladesh.

BACKGROUND: To evaluate the specificity of the Crystal VC dipstick test for detecting cholera. METHODS: We compared direct testing using the Crystal VC dipstick test and testing after enrichment for 6 h in alkaline peptone water (APW) to bacterial culture as the gold standard. Samples positive by dipstick but negative by culture were also tested using PCR. RESULTS: Stool was collected from 125 patients. The overall specificities of the direct testing and testing after 6-h enrichment in APW compared to bacterial culture were 91.8% and 98.4% (P = 0.125), respectively, and the sensitivities were 65.6% and 75.0% (P = 0.07), respectively. CONCLUSION: The increase in the sensitivity of the Crystal VC kit with the use of the 6-h enrichment step in APW compared to direct testing was marginally significant. The Crystal VC dipstick had a much higher specificity than previously reported (91-98%). Therefore, this method might be a promising screening tool for cholera outbreak surveillance in resource-limited settings where elimination of false-positive results is critical.

Persistent proteinuria is associated with the occurrence of cardiovascular disease: a nationwide population-based cohort study.

Proteinuria is an important risk factor for cardiovascular disease (CVD) and acts as a surrogate marker of renal damage. This study aimed to determine the association between changes in proteinuria and the occurrence of CVD. In our study, 1,708,712 participants who consecutively underwent national health examinations from 2003-2004 (first period) to 2005-2006 (second period) were included. They were classified into four groups based on the presence of proteinuria at the two consecutive health examinations: (1) normal (0 → 0), (2) proteinuria-improved (participants who had improved proteinuria (+ 1 → 0, + 2 → ≤ +1 [0 or + 1], ≥ +3 → ≤ +2 [0, + 1 or + 2]), (3) proteinuria-progressed (0 → ≥ +1, + 1 → ≥ +2, + 2 → ≥ +3), and (4) proteinuria-persistent (+ 1 → +1, + 2 → +2, ≥ +3 → ≥ +3). We used a multivariate Cox proportional hazards model to assess the occurrence of CVD according to changes of presence and severity of proteinuria. During a median of 14.2 years of follow-up, 143,041 participants (event rate, 8.37%) with composite CVD were observed. Compared with the normal group, the risk of incident risk of CVD was increased according to the severity of proteinuria in each of the persistent, progressed, and improved groups (p for trend < 0.001). In a pairwise comparison, the risk of composite CVD in the improved (hazard ratio [HR]: 1.32, 95% confidence interval [CI]: 1.27-1.37), progressed (HR: 1.49, 95% CI: 1.44-1.54), and persistent groups (HR: 1.78, 95% CI: 1.64-1.94) were higher than that of the normal group. Furthermore, the improved group had a relatively lower risk of composite CVD compared to the persistent group (HR: 0.75, 95% CI: 0.69-0.83, p < 0.001). The incidence risk of composite CVD was associated with changes of presence and severity of proteinuria. Persistent proteinuria may be associated with increased risk of CVD, even compared with improved or progressed proteinuria status.

Changes in urine dipstick proteinuria and its relation to the risk of diabetic retinopathy and neuropathy.

BACKGROUND: Proteinuria is considered as a predictor for cardiovascular complications in diabetes mellitus (DM). However, no study has examined the association between changes in proteinuria and the risk of diabetic microvascular complications. METHODS: Study participants were 71,825 DM patients who received urine dipstick test for proteinuria both in 2003-2004 and 2006-2007. They were categorized into four groups according to changes in proteinuria over 3 years (negative: negative → negative, resolved: proteinuria ≥ 1+ → negative, incident: negative → proteinuria ≥ 1+, persistent: proteinuria ≥ 1+ → proteinuria ≥ 1+). Cox-proportional hazard model was used in assessing the adjusted hazard ratios (HR) and 95% confidence interval (CI) for incidence of retinopathy, and neuropathy (adjusted HR [95% CI]). RESULT: In all of DM patients, risk for comprehensive incidence of retinopathy and neuropathy increased in all types of proteinuria changes. In type 1 DM, HR for retinopathy and neuropathy generally increased in order of negative (reference), resolved (2.175 [1.150-4.114] and 1.335 [0.909-1.961]), incident (2.088 [1.185-3.680] and 1.753 [1.275-2.409]), and persistent proteinuria (1.314 [0.418-4.134] and 2.098 [1.274-3.455]). This pattern of relationship was similarly observed in type 2 DM for retinopathy and neuropathy: negative (reference), resolved (1.490 [1.082-2.051] and 1.164 [0.988-1.371]), incident (1.570 [1.161-2.123] and 1.291 [1.112-1.500]), and persistent proteinuria (2.309 [1.407-3.788] and 1.272 [0.945-1.712]). CONCLUSION: Risk for diabetic retinopathy and neuropathy generally increased in order of negative, resolved, incident, and persistent proteinuria. Once manifested proteinuria was associated with the increased risk of diabetic retinopathy and neuropathy even after remission of proteinuria.

Noninvasive rapid urinary trypsinogen-2 dipstick test for early exclusion of post-endoscopic retrograde cholangiopancreatography pancreatitis within hours after endoscopic retrograde cholangiopancreatography: Clinical diagnosis and considerations.

Objective: Few reports have explored the application of urinary trypsinogen-2 measurement in the early diagnosis of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis, and none have demonstrated the benefits of noninvasive testing. This study aimed to evaluate the clinical application of the rapid urinary trypsinogen-2 dipstick test (Nipro, Japan) compared with serum amylase and lipase levels for the early diagnosis of post-ERCP pancreatitis (PEP). Methods: A total of 100 consecutive patients (54 men and 46 women) who were admitted and underwent ERCP at Tokyo Medical University Hospital from August 2021 to December 2021 were recruited. All patients underwent rapid urinary trypsinogen-2 measurement using the dipstick test before and after ERCP. Measurements were taken 24 h before ERCP for pre-ERCP and 1-4 h after ERCP for post-ERCP. Additionally, serum amylase and lipase levels were measured at 8:00 a.m. of the day after ERCP (at least 8 h after ERCP), and their diagnostic abilities for PEP were compared and evaluated. Results: PEP occurred in 5/100 patients (5%). The sensitivity, specificity, positive predictive value, and negative predictive value of the dipstick test for diagnosing PEP were 100%, 83.2%, 23.8%, and 100%, respectively. These results were comparable to the diagnostic performance of serum amylase and lipase levels at 8:00 a.m. on the day after ERCP (at least 8 h after ERCP). However, false positives must be considered. Conclusion: The dipstick test may be useful in clinical practice as a noninvasive screening test for the early prediction of PEP.